Electrode device with elongated electrode

ABSTRACT

Apparatus is provided for applying current to a nerve. A cathode is adapted to be placed in a vicinity of a cathodic longitudinal site of the nerve and to apply a cathodic current to the nerve. A primary inhibiting anode is adapted to be placed in a vicinity of a primary anodal longitudinal site of the nerve and to apply a primary anodal current to the nerve. A secondary inhibiting anode is adapted to be placed in a vicinity of a secondary anodal longitudinal site of the nerve and to apply a secondary anodal current to the nerve, the secondary anodal longitudinal site being closer to the primary anodal longitudinal site than to the cathodic longitudinal site.

CROSS-REFERENCES TO RELATED APPLICATIONS

The present patent application is a divisional of U.S. Ser. No.13/271,720, filed Oct. 12, 2011, which is a continuation of U.S. Ser.No. 11/981,301, filed Oct. 30, 2007, now U.S. Pat. No. 8,065,021, whichis a continuation of U.S. Ser. No. 10/948,516, filed Sep. 23, 2004, nowU.S. Pat. No. 7,346,398, which is a continuation of U.S. Ser. No.10/205,474, filed Jul. 24, 2002, now U.S. Pat. No. 6,907,295, which (a)claims the benefit of U.S. Provisional Application No. 60/383,157, filedMay 23, 2002, which is assigned to the assignee of the present patentapplication and is incorporated herein by reference, and (b) is relatedto U.S. Ser. No. 10/205,475, filed Jul. 24, 2002, entitled, “Selectivenerve fiber stimulation for treating heart conditions,” which isassigned to the assignee of the present patent application and isincorporated herein by reference.

This application claims the benefit of U.S. Provisional PatentApplication 60/383,157 to Ayal et al., filed May 23, 2002, entitled,“Inverse recruitment for autonomic nerve systems,” which is assigned tothe assignee of the present patent application and is incorporatedherein by reference.

This application is related to a US patent application to Gross et al.,filed on even date, entitled, “Selective nerve fiber stimulation fortreating heart conditions,” which is assigned to the assignee of thepresent patent application and is incorporated herein by reference.

FIELD OF THE INVENTION

The present invention relates generally to electrical stimulation oftissue, and specifically to methods and devices for regulating thestimulation of nerves.

BACKGROUND OF THE INVENTION

As defined by Rattay, in the article, “Analysis of models forextracellular fiber stimulation,” IEEE Transactions on BiomedicalEngineering, Vol. 36, no. 2, p. 676, 1989, which is incorporated hereinby reference, the activation function (AF) is the second spatialderivative of the electric potential along an axon. In the region wherethe activation function is positive, the axon depolarizes, and in theregion where the activation function is negative, the axonhyperpolarizes. If the activation function is sufficiently positive,then the depolarization will cause the axon to generate an actionpotential; similarly, if the activation function is sufficientlynegative, then local blocking of action potentials transmission occurs.The activation function depends on the current applied, as well as thegeometry of the electrodes and of the axon.

For a given electrode geometry, the equation governing the electricalpotential is:∇(σ∇U)=4πj,

where U is the potential, σ is the conductance tensor specifying theconductance of the various materials (electrode housing, axon,intracellular fluid, etc.), and j is a scalar function representing thecurrent source density specifying the locations of current injection.The activation function is found by solving this partial differentialequation for U. If the axon is defined to lie in the z direction, thenthe activation function is:

${AF} = {\frac{\partial^{2}U}{\partial z^{2}}.}$

In a simple, illustrative example of a point electrode located adistance d from the axis of an axon in a uniformly-conducting mediumwith conductance σ, the two equations above are solvable analytically,to yield:

${{AF} = {\frac{I_{el}}{4{\pi\sigma}} \cdot \frac{{2z^{2}} - d^{2}}{\left( {z^{2} + d^{2}} \right)^{2.5}}}},$

where I_(el) is the electrode current. It is seen that when σ and d areheld constant, and for a constant positive I_(el) (to correspond toanodal current), the minimum value of the activation function isnegative, and is attained at z=0, i.e., at the point on the nerveclosest to the source of the anodal current. Thus, the most negativepoint on the activation function corresponds to the place on a nervewhere hyperpolarization is maximized, namely at the point on the nerveclosest to the anode.

Additionally, this equation predicts positive “lobes” for the activationfunction on either side of z=0, these positive lobes peaking in theirvalues at a distance which is dependent on each of the other parametersin the equation. The positive values of the activation functioncorrespond to areas of depolarization, a phenomenon typically associatedwith cathodic current, not anodal current. However, it has been shownthat excess anodal current does indeed cause the generation of actionpotentials adjacent to the point on a nerve corresponding to z=0, andthis phenomenon is therefore called the “virtual cathode effect.” (Ananalogous, but reverse phenomenon, the “virtual anode effect” existsresponsive to excess cathodic stimulation.)

U.S. Pat. No. 6,230,061 to Hartung, which is incorporated herein byreference, describes an electrode arrangement for stimulating the heartby means of: (a) an implantable cardiac pacemaker, (b) a firstelectrode, coupled to a first output of the pacemaker via anintracardiac electrode line, and (c) a second electrode, fortransmitting electrical stimulation pulses to the heart tissue, coupledto a second output of the pacemaker via the electrode line. The voltagepulses at the two electrodes have differing polarities relative to athird electrode. The first and second electrodes are arranged on theelectrode line in such a way that the electrical dipole field whichforms is distorted towards the stimulation point in such a way that araised gradient above the stimulus threshold is formed there.

A number of patents and articles describe methods and devices forstimulating nerves to achieve a desired effect. Often these techniquesinclude a design for an electrode or electrode cuff.

U.S. Pat. No. 4,608,985 to Crish et al. and U.S. Pat. No. 4,649,936 toUngar et al., which are incorporated herein by reference, describeelectrode cuffs for selectively blocking orthodromic action potentialspassing along a nerve trunk, in a manner intended to avoid causing nervedamage.

PCT Patent Publication WO 01/10375 to Felsen et al., which isincorporated herein by reference, describes apparatus for modifying theelectrical behavior of nervous tissue. Electrical energy is applied withan electrode to a nerve in order to selectively inhibit propagation ofan action potential.

U.S. Pat. No. 5,755,750 to Petruska et al., which is incorporated hereinby reference, describes techniques for selectively blocking differentsize fibers of a nerve by applying direct electric current between ananode and a cathode that is larger than the anode.

The following articles, which are incorporated herein by reference, maybe of interest:

-   Ungar I J et al., “Generation of unidirectionally propagating action    potentials using a monopolar electrode cuff,” Annals of Biomedical    Engineering, 14:437-450 (1986)-   Sweeney J D et al., “An asymmetric two electrode cuff for generation    of unidirectionally propagated action potentials,” IEEE Transactions    on Biomedical Engineering, vol. BME-33(6) (1986)-   Sweeney J D et al., “A nerve cuff technique for selective excitation    of peripheral nerve trunk regions,” IEEE Transactions on Biomedical    Engineering, 37(7) (1990)-   Naples G G et al., “A spiral nerve cuff electrode for peripheral    nerve stimulation,” by IEEE Transactions on Biomedical Engineering,    35(11) (1988)-   van den Honert C et al., “Generation of unidirectionally propagated    action potentials in a peripheral nerve by brief stimuli,” Science,    206:1311-1312 (1979)-   van den Honert C et al., “A technique for collision block of    peripheral nerve: Single stimulus analysis,” MP-11, IEEE Trans.    Biomed. Eng. 28:373-378 (1981)-   van den Honert C et al., “A technique for collision block of    peripheral nerve: Frequency dependence,” MP-12, IEEE Trans. Biomed.    Eng. 28:379-382 (1981)-   Rijkhoff N J et al., “Acute animal studies on the use of anodal    block to reduce urethral resistance in sacral root stimulation,”    IEEE Transactions on Rehabilitation Engineering, 2(2):92 (1994)-   Mushahwar V K et al., “Muscle recruitment through electrical    stimulation of the lumbo-sacral spinal cord,” IEEE Trans Rehabil    Eng, 8(1):22-9 (2000)-   Deurloo K E et al., “Transverse tripolar stimulation of peripheral    nerve: a modelling study of spatial selectivity,” Med Biol Eng    Comput, 36(1):66-74 (1998)-   Tarver W B et al., “Clinical experience with a helical bipolar    stimulating lead,” Pace, Vol. 15, October, Part II (1992)

In physiological muscle contraction, nerve fibers are recruited in theorder of increasing size, from smaller-diameter fibers to progressivelylarger-diameter fibers. In contrast, artificial electrical stimulationof nerves using standard techniques recruits fibers in a larger- tosmaller-diameter order, because larger-diameter fibers have a lowerexcitation threshold. This unnatural recruitment order causes musclefatigue and poor force gradation. Techniques have been explored to mimicthe natural order of recruitment when performing artificial stimulationof nerves to stimulate muscles.

Fitzpatrick et al., in “A nerve cuff design for the selective activationand blocking of myelinated nerve fibers,” Ann. Conf. of the IEEE Eng. inMedicine and Biology Soc, 13(2), 906 (1991), which is incorporatedherein by reference, describe a tripolar electrode used for musclecontrol. The electrode includes a central cathode flanked on itsopposite sides by two anodes. The central cathode generates actionpotentials in the motor nerve fiber by cathodic stimulation. One of theanodes produces a complete anodal block in one direction so that theaction potential produced by the cathode is unidirectional. The otheranode produces a selective anodal block to permit passage of the actionpotential in the opposite direction through selected motor nerve fibersto produce the desired muscle stimulation or suppression.

The following articles, which are incorporated herein by reference, maybe of interest:

-   Rijkhoff N J et al., “Orderly recruitment of motoneurons in an acute    rabbit model,” Ann. Conf. of the IEEE Eng., Medicine and Biology    Soc., 20(5):2564 (1998)-   Rijkhoff N J et al., “Selective stimulation of small diameter nerve    fibers in a mixed bundle,” Proceedings of the Annual Project Meeting    Sensations/Neuros and Mid-Term Review Meeting on the TMR-Network    Neuros, Apr. 21-23, 1999, pp. 20-21 (1999)-   Baratta R et al., “Orderly stimulation of skeletal muscle motor    units with tripolar nerve cuff electrode,” IEEE Transactions on    Biomedical Engineering, 36(8):836-43 (1989)

The following articles, which are incorporated herein by reference,describe techniques using point electrodes to selectively exciteperipheral nerve fibers distant from an electrode without exciting nervefibers close to the electrode:

-   Grill W M et al., “Inversion of the current-distance relationship by    transient depolarization,” IEEE Trans Biomed Eng, 44(1):1-9 (1997)-   Goodall E V et al., “Position-selective activation of peripheral    nerve fibers with a cuff electrode,” IEEE Trans Biomed Eng,    43(8):851-6 (1996)-   Veraart C et al., “Selective control of muscle activation with a    multipolar nerve cuff electrode,” IEEE Trans Biomed Eng,    40(7):640-53 (1993)

SUMMARY OF THE INVENTION

It is an object of some aspects of the present invention to provideimproved apparatus and methods for stimulating a nerve.

It is a further object of some aspects of the present invention toprovide improved methods and apparatus for configuring an electrodeassembly.

It is still a further object of some aspects of the present invention toprovide improved methods and apparatus for driving an electrode assemblyto apply current to a nerve.

In preferred embodiments of the present invention, an electrode assemblyfor applying current to a nerve comprises a cathode, a primaryinhibiting anode and a secondary inhibiting anode, which are fixedwithin a housing. The cathode, near one end of the housing, is placed onor near the nerve, over a “cathodic longitudinal site” of the nerve, andis driven by a control unit to apply a cathodic current to the nerve.The primary inhibiting anode, adjacent to the cathode in the housing, isplaced on or over a “primary anodal longitudinal site” of the nerve, andis driven to apply a primary anodal current to the nerve. The secondaryinhibiting anode, which is separated from the cathode by the primaryinhibiting anode, is placed on or over a “secondary anodal longitudinalsite” of the nerve, and applies a secondary anodal current to the nerve.

Typically, the cathodic current applied at the cathodic longitudinalsite stimulates fibers within the nerve to generate action potentialswhich travel in both directions within the nerve—i.e., towards theanodes (“the anodal direction”), and in the opposite direction, out ofthe housing, towards a target (“the target direction”). The anodalcurrent, by contrast, is typically applied so as to inhibit the actionpotentials which were generated at the cathodic longitudinal site andwhich subsequently traveled in the anodal direction.

For most applications, the secondary anodal current is of lowermagnitude than the primary anodal current. In this manner, the “virtualcathode” effect induced by the primary anodal current is minimized. Asdescribed in the Background section of the present patent application,the virtual cathode effect can stimulate—rather than block—thegeneration of action potentials in fibers in a region adjacent to theapplication of anodal current of a sufficiently high magnitude. Inaccordance with a preferred embodiment of the present invention,application of the primary and secondary anodal currents in appropriateratios is configured to generally minimize the virtual cathode effect.Typically, but not necessarily, the ratio of the primary to thesecondary anodal current ranges from 5:1 to 10:1.

In a preferred embodiment, a tertiary inhibiting anode is employed toreduce any virtual cathode effect which may be induced by the secondaryinhibiting anode. For example, relative to a normalized cathodic currentof −1, the primary inhibiting anode, secondary inhibiting anode, andtertiary inhibiting anode may be configured to apply respective currentsof 0.66, 0.25, and 0.09. For some applications, the various anodes areindependently driven by a control unit, so as to optimize theminimization of the virtual cathode effect and the maximization (whenappropriate) of the anodally-induced hyperpolarization. Alternatively,fixed ratios are pre-defined for the currents applied by the anodes, andare set in hardware, e.g., by a set of resistors which link a singlelead coming from the control unit to the respective anodes.

In a preferred embodiment, an elongated anode replaces the anodesdescribed hereinabove. The elongated anode, when placed on or over anerve, preferably has at least two levels of electrical impedanceassociated therewith, between respective sites on the elongated anodeand the nerve. Most preferably, the portion of the elongated anodenearest the cathode has a lower level of impedance to the nerve thandoes another portion of the elongated anode, further from the cathode.For some applications, the variation in impedance is achieved byapplying a coating (e.g., IrO2 or a more resistive material) inprogressively increasing thickness to the elongated anode, beginningwith a low level of the coating at the end of the elongated anode nearthe cathode. Alternatively or additionally, the geometry of theelongated anode is configured so as to effect the change in impedance asdescribed. It is noted that the impedance between any site on theelongated anode and the nerve is a function not only of the propertiesof the anode itself, but also of the biological material which naturallypermeates the region between the nerve and the anode.

For some applications, a primary fiber-selection anode is incorporatedinto the housing, adjacent to the cathode and on the other side of thehousing from the primary and secondary inhibiting anodes. (Thus, thesequence of electrodes in the housing is: primary fiber-selection anode,cathode, primary inhibiting anode, secondary inhibiting anode.) Theprimary fiber-selection anode is preferably driven to apply anodalcurrent of sufficient magnitude to block cathode-induced actionpotential propagation in some fibers, generally the larger fibers, whichare more sensitive to the anodal current. If the current applied by theprimary fiber-selection anode is not too high, then less-sensitivefibers, typically the smaller fibers in the nerve, are not blocked bythe anodal current. Therefore, action potentials induced by the cathodecontinue to propagate in the smaller fibers, past the primaryfiber-selection anode and out of the housing. By increasing the currentdriven through the primary fiber-selection anode, progressively smallerfibers are inhibited from propagating action potentials. Conversely, bydecreasing the application of current through the primaryfiber-selection anode, larger fibers are able to propagate actionpotentials, until, in the limit where the primary fiber-selectionanode's current is zero, all fibers stimulated by the cathode conveytheir action potentials out of the housing and towards the target.

In a preferred embodiment, a secondary fiber-selection anode is alsoincorporated into the housing, adjacent to the primary fiber-selectionanode and on the far side of the cathode. (Thus, the sequence ofelectrodes in the housing is: secondary fiber-selection anode, primaryfiber-selection anode, cathode, primary inhibiting anode, secondaryinhibiting anode.) In a fashion analogous to that described hereinabovewith respect to the secondary inhibiting anode, the secondaryfiber-selection anode is preferably driven to apply a current to thenerve smaller than that applied by the primary fiber-selection anode, soas to counteract the virtual cathode effect which would otherwise, insome circumstances, induce action potential propagation responsive tothe current applied by the primary fiber-selection anode.

In preferred embodiments of the present invention, an electrode assemblyfor applying current to a nerve having a longitudinal axis comprises ahousing, adapted to be placed in a vicinity of the nerve and a cathodeand an anode, fixed to the housing. The cathode and anode are attachedto the housing such that, when the housing is placed in the vicinity ofthe nerve, both the distance of the cathode and the distance of theanode to the axis are at least approximately 1.5 times greater than theradius of the nerve. By placing the cathode and anode at such adistance, increased electrical field uniformity is obtained within thenerve. In particular, the activation function (as defined in theBackground section of this application) varies only relatively littleacross the cross-section of the nerve. This, in turn, increases theability of a control unit driving the cathode and anode to assure thatmost fibers within the nerve will experience generally the same level ofapplied currents.

In preferred embodiments of the present invention, an electrode assemblyis provided for applying current to a nerve having a radius and alongitudinal central axis. The electrode assembly comprises a housing,which is placed in a vicinity of the nerve, and first and secondelectrodes, fixed to the housing. An insulating element is fixed to thehousing between the first and second electrodes so as to define acharacteristic closest “insulating element distance” to the central axisthat is at least approximately 1.5 times greater than the radius of thenerve. Typically, the electrodes are located at the same distance fromthe central axis or at a greater distance therefrom. In a preferredembodiment, the face of each electrode is located at a distance from thecentral axis less than or equal to the closest insulating elementdistance plus the width (i.e., the longitudinal extent along the nerve)of the electrode. In a preferred embodiment, the width of each electrodeis approximately one half of the radius of the nerve.

Although many geometrical configurations are suitable for applying theprinciples of the present invention, the housings, electrodes, andinsulating elements described herein are typically generallycylindrical, i.e., having circular cross-sections. Alternatively oradditionally, at least some of these components are located at discretelocations with respect to the axis of the nerve (e.g., a singleelectrode located at “12 o'clock,” or four electrodes or insulatingelements may be evenly distributed around the axis).

In preferred embodiments of the present invention, an electrode assemblyfor applying current to a nerve comprises a cathode and a plurality ofanodes. The cathode is placed in a vicinity of a cathodic site of thenerve, and the plurality of anodes are placed in a vicinity ofrespective anodal longitudinal sites of the nerve. The plurality ofanodes apply respective anodal currents to the nerve, that define, incombination, an anodal activation function having a depolarizationportion and a hyperpolarization portion. For many applications of thepresent invention, the hyperpolarization portion is the “desired”portion of the anodal activation function. For example, thehyperpolarization portion may be configured to block action potentialpropagation in a particular direction.

By contrast, it is desired when performing many of these applications tominimize the depolarization portion of the anodal activation function,because the location on the nerve of the depolarization portioncorresponds to the location of the virtual cathode describedhereinabove. If no countermeasures would be taken, the virtual cathodecould be associated with an undesired stimulation of fibers in the nerveunder the virtual cathode. The virtual cathode effect could be minimizedto some extent by reducing the anodal current, but, if in excess, thiswould result in a decrease in the magnitude of the (typically desired)hyperpolarization region. If the anodal current is only minimallyreduced, in order to avoid adversely decreasing the magnitude of thehyperpolarization region, then the virtual cathode effect wouldtypically still be present. The inventors have determined that for manyelectrode configurations, there is no suitable balance, i.e., either thevirtual cathode effect will be reduced to a desired level, or thehyperpolarization portion of the activation function will be maintainedat a sufficiently high magnitude.

To address this issue, the plurality of anodes provided by theseembodiments of the present invention are preferably configured so as tohave the maximum magnitude of the hyperpolarization portion be at leastfive times greater than the maximum magnitude of the depolarizationamplitude. In this manner, the desired hyperpolarization effect ispreserved, and the extent of depolarization due to the anodal current isminimized. Preferably, this ratio of anodally-induced hyperpolarizationto depolarization is attained by using one or more of the following: (a)one or more secondary inhibiting anodes, as described hereinabove, tominimize the virtual cathode effect, (b) one or more insulating elementswhose closest approach to the nerve generally remains further from thecentral axis of the nerve than approximately 1.5 times the radius of thenerve, or (c) electrodes, whose closest approach to the nerve generallyremains further from the central axis of the nerve than approximately1.5 times the radius of the nerve.

In preferred embodiments of the present invention, an electrode assemblyfor applying current to a nerve having a longitudinal axis, comprisestwo or more electrodes, adapted to be placed in a vicinity of alongitudinal site of the nerve, at respective positions around the axis.If there are only two electrodes, then the control unit preferablyalternates the direction of driving a current between the two electrodesat a rate greater than 1000 Hz.

When there are three or more electrodes, thereby defining a ring ofelectrodes, the control unit preferably cycles around the electrodes inaccordance with a stimulation protocol. For example, one such protocolfor three electrodes may include driving current between electrodes 1and 2, then 2 and 3, then 3 and 1, then 1 and 2, etc., cycling throughthe combinations at an electrode-pair transition average rate of greaterthan 1000 Hz, or, for some applications, greater than 10,000 Hz. Forlarger numbers of electrodes, e.g., 6, 12, or 24, the stimulationcycling protocol is typically more complex, and is preferably configuredto cause current to pass through or close to most or all fibers in thenerve at the longitudinal site where the ring of electrodes is placed.One such complex protocol includes effectively creating a star out ofthe current lines passing through the nerve, or ensuring that eachelectrode in the ring conveys current to some, most, or all of the otherelectrodes.

Advantageously, due to the very high application rate of the currentfrom the different electrodes compared to the relatively-low biologicalresponse rate of the fibers within the nerve, the fibers at thatlongitudinal site are effectively all stimulated at substantially thesame time. In this manner, a single wave of action potential propagationis initiated from the longitudinal site at substantially the same time,and can be subsequently manipulated at other sites on the nerve usingtechniques described herein or in one or more of the patent applicationscited herein that are assigned to the assignee of the present patentapplication and are incorporated herein by reference. Further, unlikesolid ring electrodes which surround the nerve and conduct a significantportion of their current outside of the nerve, directly to the anode orcathode adjacent thereto, a larger portion of the current is conveyedinto the nerve itself using the stimulation protocols described herein.From the “perspective” of the nerve, which functions at ratesconsiderably slower than the switching rate of the ring of electrodes,it is as if a large portion of its nerve fibers were simultaneouslystimulated.

In preferred embodiments of the present invention, an electrode assemblyfor applying current to a nerve having a longitudinal axis comprises aring of two or more cathodes and a ring of two or more anodes, each ringof electrodes adapted to be placed around the nerve axis, at arespective cathodic or anodal longitudinal site of the nerve.Preferably, a control unit drives an anode in the ring of anodes todrive current through the nerve to a cathode typically at anotherorientation with respect to the axis, in order to stimulate fibers inthe nerve nearer the cathode. Thus, for example, if each ring has twelveelectrodes, then in one preferred stimulation protocol, the anode at “12o'clock” with respect to the axis drives current generally through thenerve to the cathode at 6 o'clock. After a very short delay (typically10-100 microseconds), the anode at 1 o'clock drives current generallythrough the nerve to the cathode at 7 o'clock. The pattern is preferablycontinued for all of the electrodes. It will be appreciated by one whohas read the disclosure of the present patent application that a varietyof stimulation protocols may be developed, and that a suitable protocolshould typically be determined in accordance with the anatomy of thenerve, the types of nerve fibers therein, and the purpose of thestimulation, among other factors.

There is therefore provided, in accordance with a preferred embodimentof the present invention, apparatus for applying current to a nerve,including:

a cathode, adapted to be placed in a vicinity of a cathodic longitudinalsite of the nerve and to apply a cathodic current to the nerve;

a primary inhibiting anode, adapted to be placed in a vicinity of aprimary anodal longitudinal site of the nerve and to apply a primaryanodal current to the nerve; and

a secondary inhibiting anode, adapted to be placed in a vicinity of asecondary anodal longitudinal site of the nerve and to apply a secondaryanodal current to the nerve, the secondary anodal longitudinal sitebeing closer to the primary anodal longitudinal site than to thecathodic longitudinal site.

In a preferred embodiment, the apparatus is adapted to be placed on thenerve such that, relative to the anodal longitudinal sites, the cathodiclongitudinal site is proximal to a brain of a subject, the subjectincluding the nerve. Alternatively, the apparatus is adapted to beplaced on the nerve such that, relative to the anodal longitudinalsites, the cathodic longitudinal site is distal to a brain of a subject,the subject including the nerve.

In a preferred embodiment, the primary inhibiting anode is adapted toapply the primary anodal current to the nerve so as to block propagationof action potentials past the primary anodal longitudinal site.

For some applications, the primary inhibiting anode is adapted to applythe primary anodal current to the nerve so as to block propagation pastthe primary anodal longitudinal site of action potentials in a first setof nerve fibers, and to allow propagation past the primary anodallongitudinal site of action potentials in a second set of nerve fibers,the second set of nerve fibers having characteristic diameters generallysmaller than characteristic diameters of the nerve fibers in the firstset.

In a preferred embodiment, the cathode includes a plurality of cathodes,placed in the vicinity of the cathodic longitudinal site of the nerve,at respective positions around an axis of the nerve. In this case, theplurality of cathodes are preferably adapted to apply the cathodiccurrent at a characteristic frequency greater than 1000 Hz.

Preferably, the apparatus includes a primary insulating element disposedbetween the cathode and the primary inhibiting anode. The primaryinsulating element is typically disposed in a position with respect tothe cathode and the primary inhibiting anode so as to guide the flow ofcurrent between the cathode and the primary inhibiting anode. For someapplications, the apparatus includes a secondary insulating element,disposed between the primary inhibiting anode and the secondaryinhibiting anode. In this case, a characteristic size of the secondaryinsulating element is preferably smaller than a characteristic size ofthe primary insulating element. Alternatively or additionally, acharacteristic distance of the secondary insulating element to an axisof the nerve is greater than a characteristic distance of the primaryinsulating element to the axis of the nerve.

In some preferred embodiments, the apparatus includes a tertiaryinhibiting electrode, adapted to be placed in a vicinity of a tertiaryanodal longitudinal site of the nerve and to apply a tertiary anodalcurrent to the nerve, the tertiary anodal longitudinal site being closerto the secondary anodal longitudinal site than to the primary anodallongitudinal site. In a preferred embodiment, the tertiary inhibitinganode is configured such that a current density of the tertiary anodalcurrent is of lower magnitude than a magnitude of a current density ofthe secondary anodal current.

Preferably, the apparatus includes a housing, coupled to the cathode,the primary inhibiting anode and the secondary inhibiting anode, adaptedto facilitate placement of the cathode and the anodes in the vicinitiesof their respective sites. In a preferred embodiment, the housing isconfigured such that an arc, defined by an extent that the housing isadapted to surround the nerve, is between about 90 and 270 degrees.Alternatively, the housing is configured such that an arc, defined by anextent that the housing is adapted to surround the nerve, is betweenabout 270 and 359 degrees.

Typically, a closest cathode distance to an axis of the nerve, a closestprimary inhibiting anode distance to the axis, and a closest secondaryinhibiting anode distance to the axis are all at least approximately 1.5times greater than the radius of the nerve.

For some applications, the secondary inhibiting anode is configured suchthat a secondary anodal current density induced by the secondary anodalcurrent is of lower magnitude than a magnitude of a primary anodalcurrent density induced by the primary anodal current. In a preferredembodiment, the primary anodal current is substantially of the samemagnitude as the secondary anodal current. In a preferred embodiment, acharacteristic surface area of the secondary inhibiting anode is higherthan a characteristic surface area of the primary inhibiting anode. Forexample, the characteristic surface area of the secondary inhibitinganode may be at least 2 times higher than the characteristic surfacearea of the primary inhibiting anode.

In a preferred embodiment, the secondary inhibiting anode is configuredsuch that a current density of the secondary anodal current is of lowermagnitude than a magnitude of a current density of the primary anodalcurrent. In this case, a characteristic surface area of the primaryinhibiting anode may be higher than a characteristic surface area of thesecondary inhibiting anode, and a common voltage may be applied to theprimary inhibiting anode and to the secondary inhibiting anode.

For some applications:

(a) the primary inhibiting anode is adapted to have associated therewitha primary level of electrical impedance between the primary inhibitinganode and the nerve, when in the vicinity of the primary anodallongitudinal site, and

(b) the secondary inhibiting anode is adapted to have associatedtherewith a secondary level of electrical impedance between thesecondary inhibiting anode and the nerve when in the vicinity of thesecondary anodal longitudinal site, the secondary level of impedancehaving a higher magnitude than the primary level of impedance.

In a preferred embodiment, the secondary inhibiting anode is adapted tobe coupled to the housing so as to define a secondary anode distance toan axis of the nerve, and wherein the primary inhibiting anode isadapted to be coupled to the housing so as to define a primary anodedistance to the axis of the nerve that is smaller than the secondaryanode distance. For example, a ratio of the secondary anode distance tothe primary anode distance may be greater than approximately 1.5:1.

In a preferred embodiment, the apparatus includes a primaryfiber-selection anode, adapted to be placed in a vicinity of a primaryfiber-selection anodal longitudinal site of the nerve that is closer tothe cathodic longitudinal site than to the primary anodal longitudinalsite. For example, the apparatus may include a secondary fiber-selectionanode, adapted to be placed in a vicinity of a secondary fiber-selectionanodal longitudinal site of the nerve that is closer to the primaryfiber-selection anodal longitudinal site than to the cathodiclongitudinal site.

Preferably, the apparatus includes a control unit, adapted to drive thecathode to apply the cathodic current to the nerve, adapted to drive theprimary inhibiting anode to apply the primary anodal current to thenerve, and adapted to drive the secondary inhibiting anode to apply thesecondary anodal current to the nerve. In one preferred embodiment, theapparatus includes a first resistive element coupled between the controlunit and the primary inhibiting anode, and a second resistive elementcoupled between the control unit and the secondary inhibiting anode, thesecond resistive element having a resistance higher than a resistance ofthe first resistive element.

For some applications, the apparatus includes exactly one lead thatleaves the control unit for coupling the control unit to the primary andsecondary inhibiting anodes. Alternatively, the apparatus includesrespective leads that leave the control unit and couple the control unitto the primary and secondary inhibiting anodes.

The control unit is typically adapted to configure a current density ofthe secondary anodal current to be of lower magnitude than a currentdensity of the primary anodal current. In a preferred embodiment, thecontrol unit is adapted to configure an amplitude of a current densityof the cathodic current to be between 1.1 and 2 times greater than anamplitude of a current density of the primary anodal current.Alternatively or additionally, the control unit is adapted to configurean amplitude of a current density of the cathodic current to be between3 and 6 times greater than an amplitude of a current density of thesecondary anodal current. Further alternatively or additionally, thecontrol unit is adapted to configure an amplitude of a current densityof the primary anodal current to be at least 2 times greater than anamplitude of a current density of the secondary anodal current.

There is also provided, in accordance with a preferred embodiment of thepresent invention, apparatus for applying current to a nerve having aradius and a longitudinal central axis, including:

a housing, adapted to be placed in a vicinity of the nerve; and

a cathode and an anode, fixed to the housing so as to define, when thehousing is placed in the vicinity of the nerve, respective closestcathode and anode distances to the axis that are both at leastapproximately 1.5 times greater than the radius of the nerve.

Preferably, the closest cathode and anode distances to the axis are bothat least approximately 2 times greater than the radius of the nerve.

In a preferred embodiment, the cathode includes a plurality of cathodes,placed in the vicinity of the cathodic longitudinal site of the nerve,at respective positions around the axis of the nerve, each of therespective positions being at a distance from the axis at least 1.5times greater than the radius of the nerve.

In a preferred embodiment, the apparatus includes an insulating elementdisposed between the cathode and the anode. A characteristic distance ofthe insulating element to the axis of the nerve is typically at least1.5 times greater than the radius of the nerve. For some applications,the distance of the anode to the axis is substantially the same as acharacteristic distance of the insulating element to the axis of thenerve. For other applications, the distance of the anode to the axis isgreater than a characteristic distance of the insulating element to theaxis of the nerve. For example, the distance of the anode to the axismay be within 30% of the characteristic distance of the insulatingelement to the axis of the nerve plus a width of the anode.

There is further provided, in accordance with a preferred embodiment ofthe present invention, apparatus for applying current to a nerve havinga radius and a longitudinal central axis, including:

a housing, adapted to be placed in a vicinity of the nerve;

first and second electrodes, fixed to the housing; and

an insulating element, fixed to the housing between the first and secondelectrodes so as to define a characteristic closest insulating elementdistance to the central axis that is at least approximately 1.5 timesgreater than the radius of the nerve.

In a preferred embodiment, the insulating element is adapted to beplaced in the vicinity of the nerve at a longitudinal site that isbetween respective longitudinal sites of the first and secondelectrodes. Alternatively, the insulating element is adapted to beplaced in the vicinity of the nerve at a site with respect to the axisof the nerve that is between respective sites of the first and secondelectrodes, with respect to the axis.

There is still further provided, in accordance with a preferredembodiment of the present invention, apparatus for applying current to anerve, including:

a cathode, adapted to be placed in a vicinity of a cathodic site of thenerve; and

a plurality of anodes, adapted to be placed in a vicinity of respectiveanodal longitudinal sites of the nerve and to apply respective anodalcurrents to the nerve, that define, in combination, an anodal activationfunction having: (a) a hyperpolarizing portion thereof having a maximumhyperpolarizing amplitude, and (b) a depolarizing portion thereof,having a maximum depolarizing amplitude corresponding to a depolarizingsite on the nerve distal with respect to the cathode to a sitecorresponding to the hyperpolarizing portion, wherein the maximumhyperpolarizing amplitude is at least five times greater than themaximum depolarizing amplitude.

In a preferred embodiment, the apparatus includes a housing to which thecathode and the plurality of anodes are coupled, wherein a distance of afirst one of the anodes to an axis of the nerve is less than a distanceof a second one of the anodes to the axis, the first one of the anodesbeing coupled to the housing closer to the cathode than the second oneof the anodes.

Alternatively or additionally, the apparatus includes a housing to whichthe cathode and the plurality of anodes are coupled, wherein a surfacearea of a first one of the anodes is less than a surface area of asecond one of the anodes, the first one of the anodes being coupled tothe housing closer to the cathode than the second one of the anodes.

Preferably, the apparatus includes a housing to which the cathode andthe plurality of anodes are coupled, and one of the anodes is positionedwithin the housing so as to reduce a virtual cathode effect induced byanother one of the anodes.

The cathode and anodes are typically disposed such that a first one ofthe anodal longitudinal sites is between the cathodic site and a secondone of the anodal longitudinal sites. In a preferred embodiment, theanodes are disposed such that the second one of the anodal longitudinalsites is between the first one of the anodal longitudinal sites and athird one of the anodal longitudinal sites. Preferably, the anodes areadapted such that a current density of the anodal current applied at thesecond one of the anodal longitudinal sites has a lower magnitude than amagnitude of a current density of the anodal current applied at thefirst one of the anodal longitudinal sites.

For some applications, the anodes are adapted such that a ratio of thecurrent density of the anodal current applied at the first site to thecurrent density of the anodal current applied at the second site is atleast 2:1. Preferably, the anodes are adapted such that a ratio of thecurrent density of the anodal current applied at the first site to thecurrent density of the anodal current applied at the second site is atleast 5:1.

There is yet further provided, in accordance with a preferred embodimentof the present invention, apparatus for applying current to a nerve,including:

a cathode, adapted to be placed in a vicinity of a first longitudinalsite of the nerve; and

an elongated anode, adapted to be placed in a vicinity of a secondlongitudinal site of the nerve, and, when so placed, to have associatedtherewith: (a) a first level of electrical impedance between the nerveand a location on the elongated anode proximal to the cathode, and (b) asecond level of electrical impedance, greater than the first level,between the nerve and a location on the elongated anode distal to thecathode.

Preferably, the apparatus includes a coating disposed on a surface ofthe elongated anode, configured to provide the first and second levelsof impedance. In a preferred embodiment, the coating is disposed on thesurface in different respective thicknesses at the two locations on theelongated anode. Alternatively or additionally, the coating includes acoating that has undergone a surface treatment, and wherein the coatingis configured to provide the first and second levels of impedanceresponsive to having undergone the surface treatment. In a preferredembodiment, the coating includes iridium oxide, titanium nitrite, and/orplatinum iridium.

There is also provided, in accordance with a preferred embodiment of thepresent invention, apparatus for applying current to a nerve having alongitudinal axis, including:

two or more electrodes, adapted to be placed in a vicinity of alongitudinal site of the nerve, at respective positions around the axis;and

a control unit, adapted to:

(a) drive current between two of the electrodes, thereby defining afirst pair of the electrodes and a first direction of current flow, and,less than one millisecond later,

(b) drive current between two of the electrodes, thereby defining asecond pair of the electrodes and a second direction of current flow,and

(c) cycle between steps (a) and (b) at a rate greater than 1000 Hz,

wherein at least either the first pair of electrodes is different fromthe second pair of electrodes or the first direction of current flow isdifferent from the second direction of current flow.

Typically, the two or more electrodes include three or more electrodes,or four or more electrodes.

For some applications, the control unit is adapted to set the rate to begreater than 4000 Hz.

There is yet additionally provided, in accordance with a preferredembodiment of the present invention, apparatus for applying current to anerve having a longitudinal axis, including:

a set of two or more cathodes, adapted to be placed in a vicinity of acathodic longitudinal site of the nerve, at respective positions aroundthe axis; and

a set of two or more anodes, adapted to be placed in a vicinity of ananodal longitudinal site of the nerve, at respective positions aroundthe axis.

As appropriate, the two or more cathodes may include six or morecathodes, e.g., twelve or more cathodes.

The apparatus typically includes a control unit, adapted to drivecurrent between respective ones of the cathodes and respective ones ofthe anodes. The control unit is preferably adapted to cycle the currentdriving at a rate greater than 1000 Hz. In a preferred embodiment, thecontrol unit is adapted to complete a sweep of driving the currentthrough substantially all of the cathodes in less than 1000microseconds. Preferably, the control unit is adapted to complete asweep of driving the current through substantially all of the cathodesin less than 100 microseconds.

There is still additionally provided, in accordance with a preferredembodiment of the present invention, a method for applying current to anerve, including:

applying cathodic current in a vicinity of a cathodic longitudinal siteof the nerve;

applying a primary anodal current to the nerve in a vicinity of aprimary anodal longitudinal site of the nerve; and

applying a secondary anodal current to the nerve in a vicinity of asecondary anodal longitudinal site of the nerve that is closer to theprimary anodal longitudinal site than to the cathodic longitudinal site.

There is yet additionally provided, in accordance with a preferredembodiment of the present invention, a method for applying current to anerve having a radius and a longitudinal central axis, includingapplying cathodic and anodal current to the nerve from respectivecathodic and anodal current-application sites that are both located atdistances from the axis of the nerve which are at least approximately1.5 times greater than the radius of the nerve.

There is also provided, in accordance with a preferred embodiment of thepresent invention, a method for applying current to a nerve, including:

applying cathodic current in a vicinity of a cathodic site of the nerve;and

applying anodal currents in a vicinity of respective anodal longitudinalsites of the nerve, the currents defining, in combination, an anodalactivation function having: (a) a hyperpolarizing portion thereof havinga maximum hyperpolarizing amplitude, and (b) a depolarizing portionthereof, having a maximum depolarizing amplitude corresponding to adepolarizing site on the nerve distal, with respect to the cathodicsite, to a site corresponding to the hyperpolarizing portion, whereinthe maximum hyperpolarizing amplitude is at least five times greaterthan the maximum depolarizing amplitude.

There is further provided, in accordance with a preferred embodiment ofthe present invention, a method for applying current to a nerve having alongitudinal axis, including driving current between: (a) a set of twoor more cathodic sites in a vicinity of a first longitudinal site of thenerve, which are located at respective positions around the axis, and(b) a set of two or more anodal sites in a vicinity of a secondlongitudinal site of the nerve, which are located at respectivepositions around the axis.

The present invention will be more fully understood from the followingdetailed description of the preferred embodiments thereof, takentogether with the drawings, in which:

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A is a schematic, cross-sectional illustration of an electrodeassembly for applying current to a nerve, in accordance with a preferredembodiment of the present invention;

FIG. 1B is a schematic pictorial illustration of the electrode assemblyof FIG. 1A, in accordance with a preferred embodiment of the presentinvention;

FIGS. 2A and 2B are schematic, cross-sectional illustrations of otherelectrode assemblies for applying current to a nerve, in accordance withrespective preferred embodiments of the present invention;

FIGS. 3A, 3B, and 3C are schematic, cross-sectional illustrations of yetother electrode assemblies for applying current to a nerve, inaccordance with respective preferred embodiments of the presentinvention;

FIG. 4 is a schematic, cross-sectional illustration of still anotherelectrode assembly for applying current to a nerve, in accordance with apreferred embodiment of the present invention;

FIG. 5 is a schematic, pictorial illustration of an additional electrodeassembly for applying current to a nerve, in accordance with a preferredembodiment of the present invention;

FIG. 6 is a graph modeling a calculated activation function over a rangeof distances from the central axis of a nerve to which current isapplied using an electrode assembly such as that shown in FIG. 1A, inaccordance with a preferred embodiment of the present invention; and

FIG. 7 is a graph modeling a calculated activation function over aportion of the length of a nerve to which current is applied using anelectrode assembly such as that shown in FIG. 2A, in accordance with apreferred embodiment of the present invention.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

Reference is now made to FIGS. 1A and 1B. FIG. 1A is a schematic,cross-sectional illustration of an electrode assembly 20 for applyingcurrent to a nerve 30, in accordance with a preferred embodiment of thepresent invention. FIG. 1B is a schematic pictorial illustration ofelectrode assembly 20, in accordance with a preferred embodiment of thepresent invention. It is noted that although the various electrodeassemblies shown in the figures generally contain cylindricalconfigurations of their elements, other geometrical configurations, suchas non-rotationally symmetric configurations, are also suitable forapplying the principles of the present invention. In particular, ahousing 22 of the electrode assembly (and the electrodes themselves) mayform a complete circle around the nerve, or it may define an arc betweenapproximately 0 and 90 degrees, between 90 and 180 degrees, between 180and 350 degrees, or between 350 and 359 degrees around the nerve. (Onesuch preferred embodiment, shown in FIG. 1B, includes the housing andthe electrodes defining an arc of 270 degrees.)

Preferably, electrode assembly comprises a cathode 40, a primaryinhibiting anode 42, and a secondary inhibiting anode 44. Each of theseelectrodes is fixed within housing 22 of the electrode assembly.Insulating elements 24, which are typically either part of the body ofthe housing or affixed thereto, are preferably placed so as to separatethe electrodes, and to guide current from one of the electrodes towardsthe nerve prior to being taken up by another one of the electrodes.Preferably (as shown), the insulating elements are closer to nerve 30than are the electrodes. Alternatively (not shown), insulating elements24 are generally flush with the faces of the electrodes.

Typically, cathodic current driven through cathode 40 by a control unit(not shown) stimulates fibers within nerve 30 to generate actionpotentials which travel in both directions within the nerve—i.e.,towards anodes 42 and 44 (“the anodal direction”), and in the oppositedirection, out of housing 22, towards a target (“the target direction”).Anodal current driven through anode 42, by contrast, is typicallyapplied so as to inhibit the action potentials which were induced by thecathodic current, and which subsequently traveled in the anodaldirection.

For most applications, current applied by secondary inhibiting anode 44is of lower magnitude than the current applied by primary inhibitinganode 42. In this manner, the “virtual cathode” effect induced by theprimary anodal current is minimized. In accordance with a preferredembodiment of the present invention, application of the primary andsecondary anodal currents in appropriate ratios is configured togenerally minimize the virtual cathode effect. Typically, but notnecessarily, the ratio of the primary to the secondary anodal currentranges from 2:1 to 10:1.

FIG. 2A is a schematic, cross-sectional illustration of an electrodeassembly 60, in accordance with another preferred embodiment of thepresent invention. Electrode assembly 60 comprises a cathode 70, aprimary inhibiting anode 72, and a secondary inhibiting anode 74, whichare typically driven in a manner analogous to that described hereinabovewith respect to cathode 40 and primary and secondary inhibiting anodes42 and 44.

Preferably, electrode assembly 60 additionally comprises a tertiaryanode 76, which is employed to reduce any virtual cathode effect whichmay be induced by secondary inhibiting anode 74. For example, relativeto a normalized cathodic current of −1, the primary inhibiting anode,secondary inhibiting anode, and tertiary anode may be configured toapply respective currents of 0.66, 0.25, and 0.09. Typically, themagnitude of the current from the tertiary anode is sufficiently small,such that the virtual cathode effect resulting therefrom does notgenerate action potentials that interfere with the performance ofelectrode assembly 60. For some applications, however, particularly whenthe current from primary inhibiting anode 72 is relatively high,additional anodes (not shown) are provided in electrode assembly 60.

Electrode assembly 60 preferably comprises a primary fiber-selectionanode 78, adjacent to cathode 70 and on the other side of the housingfrom anodes 72, 74, and 76. The current applied by cathode 70 typicallyinduces bi-directional action potential propagation in fibers in nerve30 having a range of diameters. In order to block propagation past anode78 of those action potentials traveling in relatively larger fibers, theprimary fiber-selection anode is preferably driven to apply anodalcurrent configured to block action potential propagation in these largerfibers of nerve 30, and configured not to block action potentialpropagation in the smaller fibers. In particular, since the largerfibers are generally more sensitive to being blocked by a lower level ofanodal current than are the smaller fibers, a given level of currentapplied through fiber-selection anode 78 typically blocks actionpotentials in the larger fibers, while allowing passage of actionpotentials induced by the current from cathode 70 and traveling in thesmall fibers. Therefore, action potentials induced by the cathodecontinue to propagate in the smaller fibers, past primaryfiber-selection anode 78, out of housing 22, and towards a target site.By increasing the current driven through the primary fiber-selectionanode, progressively smaller fibers are inhibited from propagatingaction potentials. Conversely, by decreasing the application of currentthrough primary fiber-selection anode 78, larger fibers are able topropagate action potentials.

For applications in which the current applied through primaryfiber-selection anode 78 is sufficient to create a substantial virtualcathode effect, a secondary fiber-selection anode 80 is preferablyincorporated into electrode assembly 60, adjacent to the primaryfiber-selection anode and on the far side of cathode 70. In a fashionanalogous to that described hereinabove with respect to secondaryinhibiting anode 74, secondary fiber-selection anode 80 is preferablydriven to apply a current to the nerve smaller than that applied byprimary fiber-selection anode 78, so as to counteract the virtualcathode effect which would otherwise, in some circumstances, induceaction potential propagation responsive to the current applied byprimary fiber-selection anode 78.

Preferably, fixed ratios for the currents applied by anodes 72, 74, 76,78, and 80 are pre-defined and are set in hardware, e.g., by a set 82 ofresistors R1, R2, R3, R4, and R5, which couple a single lead 86 comingfrom a control unit 90 to the respective anodes. Typically, a guide tube88 conveys lead 86, in combination with a second lead 84 that drivescathode 70, from control unit 90 to electrode assembly 60.Advantageously, this embodiment provides control over multiple anodes,and corresponding reduction of the virtual cathode effect, with aminimum number of leads.

Alternatively, for some applications (not shown), particularly whencathodic and anodal current parameters vary over a wide range, thevarious anodes are independently driven by the control unit viarespective leads, so as to optimize the minimization of the virtualcathode effect and the maximization (when appropriate) ofanodally-induced hyperpolarization. For some applications, a combinationof the two techniques described are utilized, whereby, for example,anodes 72, 74, and 76 are driven by current in a single lead, and anodes78 and 80 are driven by current in two additional, separate leads.

Preferably, electrode assembly 60 (as well as the other electrodeassemblies described herein, as appropriate) has physical dimensionsconfigured so as to provide a relatively uniform activation functionacross the cross-section of nerve 30. The distance L1 separating thecentral longitudinal axis of nerve 30 from cathode 70 and from anodes72, 74, 76, 78, and 80 is typically at least approximately 1.5 timesgreater than the radius L0 of the nerve. For many applications, L1 isgreater than two times L0. By placing the cathode and anodes at suchdistances, increased electrical field uniformity is obtained within thenerve, particularly as the gradients in the activation function arelargest near the electrodes, and are significantly reduced across thecross-section of the nerve. This, in turn, increases the ability ofcontrol unit 90 to assure that most fibers within the nerve willexperience generally the same level of applied currents.

Insulating elements 24 preferably separate cathode 70 from anodes 72 and78. For some applications, additional insulating elements 24 separatethe various adjacent anodes in electrode assembly 60. The insulatingelements define a characteristic closest “insulating element distance”L2 to the axis of nerve 30 that is preferably at least approximately 1.5times greater than L0. It will be appreciated that for structuralreasons, spokes or other offshoots of the insulating elements may comecloser to the nerve. However, the “functional” portions of theinsulating elements, i.e., those portions which provide a substantialeffect on the direction of current flow between the electrodes andthrough the nerve, preferably remain at a closest distance L2 of atleast 1.5*L0. For some applications, particularly those in which batterylife is a pressing factor, L2 is set to be less than 1.5*L0, at theexpense of some uniformity of the applied field.

Typically, L1 is greater than or equal to L2. For anode and cathodewidths w, preferred values for L1 are in the range L2<L1<1.5 (L2+w).Further preferably, L2+0.5w<L1<L2+w. Typically, the width w of theelectrodes is approximately equal to 0.5*L0. (The width w, as well asother dimensions, are not drawn to scale in the figures.) In accordancewith a preferred embodiment of the present invention, when L0 is between1 and 2 mm, L2 is preferably between 1.5 and 3 mm, L1 is between 1.5 and4 mm, and w is between 0.5 and 1 mm.

FIG. 2B is a schematic, cross-sectional illustration of an electrodeassembly 61, in accordance with another preferred embodiment of thepresent invention. Electrode assembly 61 is generally similar toelectrode assembly 60, described hereinabove with reference to FIG. 2A,except for differences as described.

Whereas in electrode assembly 60, insulating elements 24 all hadgenerally equal dimensions, electrode assembly 61 provides each of fiveinsulating elements 24A, 24B, 24C, 24D, and 24E with a respective(typically different) distance to the axis of nerve 30 of L2(A), L2(B),L2(C), L2(D), and L2(E). In general, as the distance L2(x) for any givenone of the insulating elements decreases, the current densityexperienced by the nerve in a vicinity of the insulating elementincreases. Thus, for example, in the preferred embodiment shown in FIG.2B, L2(C) corresponding to insulating element 24C is relatively large,such that the current density in the nerve near anode 76 is low.

FIG. 3A is a schematic, cross-sectional illustration of an electrodeassembly 110, in accordance with a preferred embodiment of the presentinvention. Electrode assembly 110 is analogous to electrode assembly 20,described hereinabove with reference to FIG. 1A, except for differencesas described. A cathode 120 of electrode assembly 110 serves generallythe same purpose as cathode 40, while an elongated anode 122 preferablyreplaces anodes 42 and 44. Typically, elongated anode 122 is 0.5 mm-10mm in length, although it may be longer or shorter responsive to thelevel of currents expected to be applied therethrough.

Elongated anode 122, when placed on or over nerve 30, preferably has atleast two levels of electrical impedance associated therewith, betweenrespective sites on the elongated anode and the nerve. A biologicalmaterial 92, typically including fibrous tissue and body fluids,generally occupies some of the space between the electrodes and thenerve. The impedance governing the passage of current from elongatedanode 122 to nerve 30 is therefore typically a function of theproperties of biological material 92. Additionally, a resistive element124 (e.g., a shaped iridium oxide coating, a titanium nitrite coating,or a platinum iridium coating) preferably provides greater electricalimpedance distal to cathode 120 than proximal thereto. In a preferredembodiment, the coating undergoes a surface treatment (e.g., “sandblasting” or a chemical treatment), in which the effective microscopicsurface area is increased by the treatment. Preferably, theproximal-to-the-cathode end of the coating is more heavily treated bythe surface treatment, and therefore has lower impedance. Alternativelyor additionally, the geometry of the elongated anode is configured so asto effect the change in impedance as described.

Typically, the anodal current leaving the portion of elongated anode 122distal to cathode 120 minimizes the virtual cathode effect inducedthereat by anodal current leaving the portion of elongated anode 122proximal to cathode 120.

FIG. 3B is a schematic, cross-sectional illustration of an electrodeassembly 111, in accordance with a preferred embodiment of the presentinvention. Preferably, a current density in a vicinity of a primaryanode 123 is higher than a current density in a vicinity of a secondaryanode 124. The difference in current densities is preferably attained byhaving a width w2 of anode 124 be at least 2-10 times higher than acorresponding width w1 of anode 123. In this manner, when generally thesame current is passed through both anodes, the current density—and thusthe hyperpolarizing effect on the activation function—is greater nearanode 123 than near anode 124.

FIG. 3C is a schematic, cross-sectional illustration of an electrodeassembly 112, in accordance with a preferred embodiment of the presentinvention. In this embodiment, the distance L1(B) between a primaryanode 125 and the axis of nerve 30 is preferably smaller than thedistance L1(A) between a secondary anode 126 and the axis of the nerve.The distance of cathode 120 from the axis is similar to L1(A) (asshown), while in other embodiments (not shown) the distance is closer toL1(B). In a manner similar to that described with reference to FIG. 3B,the geometrical configuration of the cathode and the anodes shown inFIG. 3C typically provides higher current density near the anode that isproximal to the cathode, and provides generally lower current densitynear the anode that is distal to the cathode.

FIG. 4 is a schematic, cross-sectional illustration of an electrodeassembly 140 surrounding nerve 30, which is driven by a control unit 160to apply current to the nerve, in accordance with a preferred embodimentof the present invention. Two or more electrodes 150 fixed to a housing142 are placed at respective positions around the axis. Typically,electrodes 150 comprise at least three, and preferably four or moreelectrodes. In this case, insulating elements 144 are preferablydisposed between adjacent electrodes. If there are only two electrodes,then control unit 160 preferably alternates the direction of the currentdriven between the two electrodes at a rate greater than 1000 Hz.

When there are three or more electrodes 150, thereby defining a ring ofelectrodes, control unit 160 preferably cycles its driving of theelectrodes in accordance with a stimulation protocol. For example, onesuch protocol for three electrodes may include driving current betweenelectrodes 1 and 2, then 2 and 3, then 3 and 1, then 1 and 2, etc.,cycling through the combinations at an average rate of greater than 1000Hz, or, for some applications, greater than 10,000 Hz. For largernumbers of electrodes, e.g., 6, 12, or 24, the stimulation cyclingprotocol is typically more complex, and is preferably configured tocause current to pass through or close to most or all fibers in thenerve at the longitudinal site where the ring of electrodes is placed.One such complex protocol includes effectively creating a star out ofsuccessive current lines passing through the nerve. In FIG. 4, aninitial set of four such lines 152, 154, 156, and 158 are shown.

FIG. 5 is a schematic, pictorial illustration of an electrode assembly170, in accordance with another preferred embodiment of the presentinvention. Electrode assembly 170 comprises an anodal ring 172 of two ormore anodes and a cathodic ring 192 of two or more cathodes. In thepreferred embodiment shown in FIG. 5, anodal ring 172 comprises anodes174, 176, 178, 180, 182, and 184, and cathodic ring 192 comprisescathodes 194, 196, 198, 200, 202, and 204. Each ring of electrodes isplaced around the nerve axis, at a respective anodal or cathodiclongitudinal site of the nerve.

Preferably, a control unit drives anode 176 to drive current throughnerve 30 to cathode 196, in order to initiate generation of actionpotentials near cathode 196 and/or near a substantial portion ofcathodic ring 192. Cathode 196 and anode 176 are preferably atmutually-opposed orientations with respect to the axis. In this manner,a greater portion of the current from anode 176 enters nerve 30 than if,for example, the control unit were to drive anode 176 to send the sameamount of charge to cathode 202. In this latter case, a substantialportion of the current leaving anode 176 would travel directly throughthe biological material surrounding nerve 30, and not enter into nerve30.

In the example shown in FIG. 5, after anode 176 sends current to cathode196, anode 178 sends current to cathode 198, and then anode 180 sendscurrent to cathode 200. Preferably, an entire sweep of all of theelectrodes in the two rings is accomplished within 0.01-1 millisecond.

Advantageously, by utilizing discrete electrodes arranged into a ring ofcathodes and a ring of anodes, each located at respective longitudinalsites on the nerve, fibers in the nerve are stimulated near the ring ofcathodes, and inhibited near the ring of anodes, typically usingsubstantially less current than if a solid anode ring and a solidcathode ring were placed around the nerve. Further advantageously,steering of current to traverse or avoid certain regions in thecross-section of the nerve is readily attainable, using the techniquesdescribed herein, by suitable activation of the cathodes and/or anodes.

For simplicity, FIG. 5 shows only a single anodal ring 172. It is notedthat the use of rings of anodes and/or a ring of cathodes is preferablyalso applied, as appropriate, in combination with thecathode—anode—anode configuration of FIGS. 1A and 1B, or in combinationwith the anode—anode—cathode—anode—anode—anode configuration of FIGS. 2Aand 2B. In a preferred embodiment, some of the electrodes (e.g., cathode70 and anodes 72 and 78) comprise multiple electrodes disposed in aring, while others of the electrodes (e.g., anodes 74, 76, and 80) aregenerally solid rings, each comprising only a single ring.

FIG. 6 is a graph modeling calculated activation function over a rangeof distances from the central axis of a nerve, in accordance with apreferred embodiment of the present invention. The graph models, in asimplified fashion, the activation function, at a cathodic site,produced in response to application of current by, for example,electrode assembly 20 (FIG. 1A) or electrode assembly 60 (FIG. 2A). Theequation producing the graph shown in FIG. 6 is:

${{{AF}(r)} = {\frac{I}{2\pi}{\int\limits_{0}^{2\pi}{\left\lbrack {1 + \left( \frac{r}{R} \right)^{2} - {2\left( \frac{r}{R} \right)\cos\;\varphi}} \right\rbrack^{- 1.5}{\mathbb{d}\varphi}}}}},$

where r is the radius from the central axis of the nerve, and R is thedistance of an electrode ring from the axis. L0 in the figure shows theradius of a typical nerve, and L2 shows the distance to an insulatingelement. As noted above, the amount of change of the activation functionwithin the nerve (r<L0) is significantly smaller than the amount ofchange of the activation function outside the nerve (r>L0).

FIG. 7 is a graph modeling calculated activation function over a portionof the length of nerve 30, when current is applied using an electrodeassembly such as that shown in FIG. 2A (without applying current throughanodes 78 and 80), in accordance with a preferred embodiment of thepresent invention. For the purposes of modeling the activation function,cathode 70 is placed at a longitudinal site on the nerve labeled z=−3(in relative units), and anodes 72, 74, and 76 are placed atlongitudinal positions z=0, 1.4, and 2.7. Anodes 72, 74, and 76 aredriven to apply currents A1=0.66, A2=0.25, and A3=0.09, respectively.Each one of the electrodes generates its own activation functionresponsive to the applied currents, as modeled in FIG. 7.

The top three data lines in FIG. 7 show that each of the anodesgenerates a depolarization portion (most clearly seen for appliedcurrent A1) and a hyperpolarization portion (clearly seen for eachanode). It is noted that the depolarization portion of the activationfunction generated by the largest applied anodal current (A1) atapproximately z=1.2 is substantial, and, in many cases, is sufficient tostimulate fibers within the nerve.

The sum of the effect of each of the anodal activation functions is seenin the fourth data line in FIG. 7, labeled “summed anodes.” This linedemonstrates that the hyperpolarization portion of the activationfunction due to anodal current A2 significantly counteracts thedepolarization portion of the activation function due to anodal currentA1. Advantageously, the peaks 222 at z>0 are generally not of sufficientmagnitude to excessively stimulate the nerve fibers within nerve 30 bymeans of the virtual cathode effect. Nevertheless, the maximumhyperpolarization peak 220 of the “summed anodes” curve remains strong,sufficient to inhibit action potential propagation in a substantialproportion of the fibers of nerve 30. The ratio of the magnitude of peak220 to the magnitude of the highest of depolarization peaks 222 istypically at least 8:1, and is preferably greater than 10:1.

The bottom data line in FIG. 7 shows the combined effect on theactivation function due to the summed anode activation function and theactivation function due to the cathode. It is noted that the use of thevarious anodes does not excessively decrease either the magnitude of thedesired depolarizing peak 230, or that of the desired hyperpolarizingpeak 240 of the combined activation function.

As appropriate, techniques described herein are practiced in conjunctionwith methods and apparatus described in one or more of the followingapplications which are assigned to the assignee of the present patentapplication and incorporated herein by reference:

-   -   a US patent application to Gross et al., filed on even date with        the present patent application, entitled, “Selective nerve fiber        stimulation for treating heart conditions,”    -   U.S. Provisional Patent Application 60/383,157 to Ayal et al.,        filed May 23, 2002, entitled, “Inverse recruitment for autonomic        nerve systems,”    -   PCT Patent Application PCT/IL02/00068 to Cohen et al., filed        Jan. 23, 2002, entitled, “Treatment of disorders by        unidirectional nerve stimulation,” which published as PCT        Publication WO 03/018113    -   U.S. patent application Ser. No. 09/944,913 to Cohen and Gross,        filed Aug. 31, 2001, entitled, “Treatment of disorders by        unidirectional nerve stimulation,” now U.S. Pat. No. 6,684,105,        and    -   U.S. patent application Ser. No. 09/824,682 to Cohen and Ayal,        filed Apr. 4, 2001, entitled “Method and apparatus for selective        control of nerve fibers,” now U.S. Pat. No. 6,600,954.

It will thus be appreciated by persons skilled in the art that thepresent invention is not limited to what has been particularly shown anddescribed hereinabove. Rather, the scope of the present inventionincludes both combinations and subcombinations of the various featuresdescribed hereinabove, as well as variations and modifications thereofthat are not in the prior art, which would occur to persons skilled inthe art upon reading the foregoing description.

The invention claimed is:
 1. Apparatus for applying current to a nerve,the apparatus comprising: a housing, which is configured to be placedaround the nerve; and an elongated electrode, which is coupled to thehousing, and which is configured to have, when placed on or over thenerve, at least two different levels of electrical impedance associatedtherewith, between respective sites on the elongated electrode and thenerve.
 2. The apparatus according to claim 1, wherein a longitudinallength of the elongated electrode is between 0.5 mm and 10 mm.
 3. Theapparatus according to claim 1, wherein the elongated electrodecomprises a resistive element that provides the at least two levels ofelectrical impedance.
 4. The apparatus according to claim 3, wherein theresistive element comprises a coating applied to the elongatedelectrode.
 5. The apparatus according to claim 4, wherein the coatinghas a progressively increasing thickness along the elongated electrodethat provides the at least two levels of electrical impedance.
 6. Theapparatus according to claim 4, wherein the coating is selected from thegroup consisting of: an iridium oxide coating, a titanium nitritecoating, and a platinum iridium coating.
 7. The apparatus according toclaim 3, wherein a geometry of the elongated electrode is configured toeffect the at least two different levels of electrical impedance.
 8. Theapparatus according to claim 1, wherein the elongated electrodecomprises an elongated anode, and wherein the apparatus furthercomprises a control unit, which is configured to drive the elongatedanode to apply an anodal current to the nerve.
 9. The apparatusaccording to claim 8, further comprising a cathode, which is coupled tothe housing, wherein the control unit is configured to drive the cathodeto apply a cathodic current to the nerve.
 10. The apparatus according toclaim 9, wherein the elongated anode is configured to have a greaterlevel of electrical impedance further from the cathode than closerthereto.
 11. The apparatus according to claim 10, wherein the coatinghas a progressively increasing thickness along the elongated anode thatprovides the at least two levels of electrical impedance, whichthickness begins with a low level of the coating at an end of theelongated anode near the cathode.
 12. The apparatus according to claim10, wherein the resistive element comprises a coating applied to theelongated element, which coating is surface treated more heavily closerto the cathode than further therefrom.
 13. The apparatus according toclaim 9, wherein the elongated anode is a first anode disposed on afirst longitudinal side of the cathode, and wherein the apparatusfurther comprises a second anode disposed on a second longitudinal sideof the cathode.